Cardiomyopathy determines the prognosis of patients with immunoglobulin light chain (AL) amyloidosis, a rare systemic disease caused by the misfolding and deposition of monoclonal light chains (LCs). The reasons underlying their cardiac tropism remain unknown, and an animal model recapitulating the main pathological features of AL amyloidosis is needed. Taking advantage of the similarities between the vertebrate cardiac muscle and Caenorhabditis elegans pharynx, we developed a new transgenic nematode expressing a human amyloidogenic λ LC, the sequence of which was deduced from a patient with AL amyloidosis with cardiac involvement (MNH). Strains expressing a non-amyloidogenic LC (MNM) or the empty vector only (MNV) were generated as controls. At variance with controls, LCs expressed in the body-wall muscle of MNH worms formed soluble dimeric assemblies, which could be secreted and reach different organs. Notably, MNH worms exerted a pharyngeal impairment resembling cardiac functional dysfunction in patients with AL amyloidosis, accompanied by increased radical oxygen species production and tissue ultrastructural damage. This new animal model could help to elucidate the mechanisms underlying the cardiac-specific toxicity occurring in AL amyloidosis, providing innovative insights into the pathophysiology.

In the complex development of various diseases, nitric oxide‑mediated S‑nitrosylation is increasingly recognized for its distinct regulatory function. Recent research has advanced our knowledge of how this nitric oxide‑dependent modification is dynamically controlled under both physiological and pathological conditions. S‑nitrosylation plays a key role in regulating mitochondrial function, gene transcription, cellular homeostasis and metabolism and it is also involved in the pathogenesis of cardiovascular disorders, neurological conditions and cancer. The present review outlined the signaling pathways driven by nitric oxide and describes the formation, specificity and factors that influence S‑nitrosylation levels. It also compared the strengths and limitations of different detection methods for S‑nitrosation reactions. The present review discussed the cellular regulatory mechanisms affected by S‑nitrosylation to clarify how certain major diseases are connected to specific S‑nitrosylated proteins. These insights may guide the development of targeted repair strategies for malfunctioning proteins by focusing on defined S‑nitrosylation sites, offering theoretical support for disease intervention and treatment.

Clonal hematopoiesis (CH) is common in the general population and associated with various health risks, but its prevalence and clinical implications in acute myeloid leukemia (AML) long-term survivors (LTS; ≥5-year survival) are unknown. We analyzed CH in 373 AML-LTS with a median 11.6-year follow-up from diagnosis using a sensitive targeted sequencing assay based on single-molecule molecular inversion probes. CH variants were detected in 61.9% of survivors, with 26% having small-clone CH (SC-CH, variant allele frequency (VAF) < 2%) and 35.9% CH of indeterminate potential (≥2% VAF). CH was more prevalent in survivors treated with chemotherapy only (75.7%) compared to those who received allogeneic stem cell transplantation (alloSCT, 54.0%) and to age group-matched healthy controls. In chemotherapy-treated survivors, CH prevalence increased with age, whereas in alloSCT recipients, it most closely associated with hematopoietic age (i.e., the sum of donor age and time since transplantation). The variant spectrum also differed by treatment, with TP53 and PPM1D variants being more common in the chemotherapy group. CH variants ≥10% VAF associated with increased risks of diabetes in alloSCT recipients and secondary neoplasms in chemotherapy-treated survivors. This study provides insights into the high prevalence and potential clinical relevance of CH in AML-LTS.

Previous studies on preoperative predictors of microvascular invasion (MVI) in intrahepatic cholangiocarcinoma (ICCA) have presented inconsistent results. This study aimed to identify preoperative clinical and magnetic resonance imaging (MRI) factors that can predict MVI in ICCA and to evaluate their prognostic utility using a multicenter cohort.

A multicenter cohort of 446 patients who underwent preoperative MRI and surgical resection for ICCA at six tertiary referral institutions between 2009 and 2018 was analyzed for clinical, pathologic, and MR imaging characteristics. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of pathologically confirmed MVI, which were subsequently used to stratify patients into low-, intermediate-, and high-risk groups based on the number of predictors identified. Kaplan-Meier survival analysis and log-rank test were conducted to assess long-term survival and early recurrence among the three groups.

Among the 446 patients (mean age, 63.0 ± 9.9 years; 277 men), 234 (52.5%) had MVI on pathology. Independent predictors of MVI included serum carbohydrate antigen 19-9 levels (≥80 U/mL; odds ratio [OR]: 2.68, 95% confidence interval [CI]: 1.64-4.37, p < 0.001), tumor size (≥4 cm; OR: 1.60, 95% CI: 1.01-2.54, p = 0.046), tumor multiplicity (OR: 2.84, 95% CI: 1.58-5.12, p < 0.001), and arterial phase peritumoral enhancement (OR: 2.83, 95% CI: 1.81-4.42, p < 0.001). Stratifying patients by MVI risk - low (no predictors), intermediate (1-3 predictors), and high (4 predictors) - revealed a significant decrease in both recurrence-free and overall survival rates (p < 0.001), along with a corresponding increase in early recurrence rates (p < 0.001) as the risk level increased.

Risk stratification utilizing four key predictors can effectively assess the risk of MVI in ICCA and is associated with postoperative outcomes.

Myeloproliferative neoplasms (MPNs) represent a group of blood disorders characterized by myeloid cell proliferation and an associated increased risk of thrombosis and bleeding. Platelet count may have a direct link to these complications.

To share our MPN clinic's experience with hemostatic testing and bleeding outcomes in patients with platelets ≥ 800 × 10⁹/L.

This was a single-center retrospective study from May 2022 to September 2024. Clinical characteristics, treatments, and bleeding events of patients with MPN or chronic myeloid leukemia were recorded. Laboratory assessments included full blood count, renal function, coagulation profiles, platelet function test, and von Willebrand factor (VWF) assays.

A total of 39 patients were included, majority of whom received aspirin for thrombosis prevention (76%). The study found that bleeding complications occurred in 33% of patients, with mucocutaneous bleeding being the most common. There was a trend toward bleeding in patients on aspirin (P = .07). However, platelet count alone did not predict bleeding risk. While some patients showed abnormal VWF function, low VWF levels were not consistently associated with increased bleeding. Interestingly, we found moderate negative correlation between baseline VWF ristocetin/antigen and activated partial thromboplastin time (P = .02; r = -.37) and prothrombin time (P = .009, r = -.45), suggesting other potential coagulation imbalances associated with bleeding diathesis in MPNs. Post cytoreduction, there was a significant increase in mean VWF ristocetin/antigen ratio (P = .0009).

The study illustrates the limitations of relying solely on platelet counts to estimate bleeding risk in MPN patients. Assessment of VWF activity and careful selection of antithrombotic therapy were highlighted as important considerations.

Cancer has remained the second leading cause of death worldwide for over a century. Despite significant advances, effectively targeting cancer cells and overcoming therapeutic challenges remain critical goals. In this review, we focus on advanced metastatic prostate tumors, where the patients' five-year survival rate is less than 35%. While standard androgen deprivation therapy (ADT) has been effective for most prostate cancer patients, recurrence of aggressive tumors is common, emphasizing an urgent need for new treatment strategies. Immunotherapy has gained attention for its potential to harness the immune system against cancer cells. Among these, oncolytic virotherapy stands out for its tumor-specific tropism, its ability to transform or convert the immune-suppressive tumor microenvironment by enhancing immune cell infiltration, and its capacity for therapeutic gene delivery. This review explores the background of commonly used viruses, evaluation models (including cell culture, animal models, ex vivo platforms, and clinical trials), and the anticipated outcomes and challenges of oncolytic virotherapy. By addressing these aspects, we aim to provide a comprehensive overview of the current state and future directions of oncolytic virotherapy models in the treatment of advanced prostate cancer.

Cell death is a crucial mechanism by which radiotherapy eliminates tumor cells. Ferroptosis, characterized by intracellular iron overload and lipid peroxidation, represents a distinct form of programmed cell death. Recent research has demonstrated that numerous malignant tumors exhibit high sensitivity to ferroptosis. Therefore, the induction of ferroptosis in tumor cells has emerged as a promising approach to overcome apoptosis resistance and increase sensitivity to radiotherapy. In this review, we aim to shed light on ferroptosis and its dual roles in both enhancing radiation sensitivity in tumor cells and facilitating radiation-induced injury. Then we discussed the contradiction of ferroptosis between radiation sensitivity and radiation-induced injury, providing valuable insights and directions for the advancement of clinical tumor radiotherapy.

Clear cell renal cell carcinoma is a common and aggressive form of renal cell carcinoma. Its incidence continues to rise, and metastatic recurrence leads to poor clinical outcomes. Current prognostic biomarkers lack reliability. We integrated multi-omics data to discover key ccRCC genes and build a prognostic model to improve risk prediction and guide treatment decisions.

Our study integrated genome-wide CRISPR screening data from DepMap and transcriptomic profiles from TCGA to identify key genes associated with ccRCC pathogenesis. Initial screening identified 11 candidate genes through differential expression analysis and CRISPR functional validation. Using LASSO and Cox regression, we selected five key genes (GGT6, HAO2, SLPI, MELK, and EIF4A1) for model construction. The functional role of MELK was tested by knockdown experiments. Additional analyses included tumor mutation burden, immune microenvironment assessment, and drug response prediction.

The model stratified patients into high-risk and low-risk groups with distinct survival outcomes. High-risk cases showed higher mutation loads, immunosuppressive features, and activated cytokine pathways, whereas low-risk cases displayed metabolic pathway activity. MELK knockdown reduced cancer cell proliferation and migration. High-risk patients exhibited better responses to targeted drugs such as pazopanib and sunitinib.

Our study demonstrates the pivotal role of MELK in ccRCC progression. This multi-omics-driven model elucidates MELK-mediated mechanisms and their interactions with the tumor microenvironment, providing novel strategies for risk stratification and targeted therapy. Future studies will validate these findings in independent cohorts and investigate the regulatory networks of MELK to identify potential therapeutic targets.

Breast cancer is one of the most common cancers among women worldwide, exhibiting notably high incidence and mortality rates. Despite its high fatality, a comprehensive study that mechanism and treatment of herbal medicines has not yet been conducted. Quercetin, a natural flavonoid, exhibits multi-targeted therapeutic potential against breast cancer. The aim of this study is to investigate and assess the mechanism and treatment of quercetin in breast cancer. We collected articles published within five years using PubMed, Google Scholar, and Web of Science with "breast cancer" and "quercetin" as keywords. Correspondingly, a total of 272 relevant articles were retrieved. Quercetin exhibits multi-modal therapeutic potential in breast cancer through its ability to orchestrate diverse molecular mechanisms, particularly in TNBC, such as targeting IGF1/IGF1R pathway, PI3K/Akt/mTOR, Wnt/β-catenin, MAPK/ERK cascades, and PTEN promoter demethylation. Critically, quercetin demonstrates synergistic activity with chemotherapy by overcoming drug resistance and reducing toxicity. Its therapeutic efficacy arises from concurrently inducing apoptosis and inhibiting proliferation, migration, invasion and metastasis. This profile positions quercetin as a strategic agent against breast cancer's complex pathophysiology, effectively disrupting breast cancer malignant progression.

Liver cancers are common malignancies that primarily include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Currently, the most commonly used serum markers for HCC are alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II), while the most commonly used serum markers for CCA are carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In recent years, many HCC diagnostic models using the combined detection of serum AFP, AFP-L3% and PIVKA-II have been established. For serum AFP, AFP-L3%, PIVKA-II and their many diagnostic models, there has been no clear guidance on the selection of these markers and their various combinations in the diagnosis of liver cancers. The aim of this study was to evaluate and compare the efficacy of these markers and the models that incorporate them in diagnosing HCC and CCA. This could assist in identifying the optimal patterns of serum AFP, AFP-L3% and PIVKA-II for the diagnosis of liver cancers.

Clinical data and the results of serum AFP, AFP-L3%, PIVKA-II, CEA and CA19-9 were collected from 117 patients with HCC, 28 patients with CCA and 101 patients with benign liver diseases. Laboratory tests and detection of serum tumor markers in liver cancer patients were conducted prior to treatments. Recently published diagnostic models for AFP, AFP-L3% and PIVKA-II detection were collected; these included GALAD, ASAP, GALAD-C, GAAP, C-GALAD, C-GALAD II and GAP-TALAD.

Levels of AFP-L3%, PIVKA-II, GALAD, ASAP, GALAD-C, GAAP, C-GALAD and C-GALAD II significantly differed between the patient cohorts, with the highest levels seen in HCC, followed by CCA and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of CEA and CA19-9 significantly differed between cohorts, with the highest levels seen in CCA, followed by HCC and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of AFP and GAP-TALAD in HCC patients were significantly higher than those in patients with CCA and patients with benign liver diseases (p < 0.05), but there were no significant differences in levels of AFP and GAP-TALAD between patients with CCA and benign liver diseases (p > 0.05). In the diagnosis of HCC, GAP-TALAD, GALAD, C-GALAD, ASAP and GALAD-C showed the highest efficacy. In the diagnosis of overall liver cancers (HCC and CCA), GALAD-C, GAAP, GALAD, ASAP and C-GALAD showed the highest efficacy. In the diagnosis of early liver cancers (early HCC and CCA), GALAD, GALAD-C, GAAP, C-GALAD and ASAP showed the highest efficacy.

For serum AFP, AFP-L3% and PIVKA-II, diagnostic models of combined marker detection improved efficacy in the diagnosis of liver cancers. Diagnostic models GALAD, ASAP, GALAD-C and C-GALAD showed the highest efficacy in the diagnosis of HCC, overall liver cancers (HCC + CCA) and early liver cancers, and can be used preferentially in clinical practice.